The Natural Flavonoid Pinocembrin: Molecular Targets and Potential Therapeutic Applications

Lan, Xi; Wang, Wenzhu; Li, Qiang; Wang, Jian

doi:10.1007/s12035-015-9125-2

Cited by 118 publications

(90 citation statements)

References 73 publications

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“…Pinocembrin acts at multiple targets (Lan et al, 2016) and has been shown to offer protection after cerebral ischemia (Shi et al, 2011; Wu et al, 2013). We demonstrated here that pinocembrin can significantly improve neurologic function, lessen brain injury volume, and decrease brain water content of ICH mice in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…Pinocembrin (purity > 99%), a kind gift from Dr. Guanhua Du (Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China), was dissolved in 20% hydroxypropyl- β -cyclodextrin (HP- β -CD, Sigma-Aldrich) as described previously (Lan et al, 2016; Liu et al, 2014). Animals were randomly assigned (http://www.randomizer.org/) to receive pinocembrin (2.5, 5, 10 mg/kg) or vehicle via tail vein (i.v.)…”

Section: Methodsmentioning

confidence: 99%

“…at 2 h after ICH and then twice daily until euthanasia. The delivery route, dosing, and treatment regimens were based on previous work (Lan et al, 2016; Zhao et al, 2014) and our pilot studies. We divided animals into four groups: 1) Sham+vehicle: mice that were injected with saline intrastriatally plus i.v.…”

Section: Methodsmentioning

confidence: 99%

“…Current data indicate that pinocembrin, which has been chemically synthesized (Lan et al, 2016), might be promising for ICH treatment. However, its efficacy in the ICH model remains to be determined because the pathogenesis of ICH is different from that of ischemic stroke.…”

Section: Introductionmentioning

confidence: 99%

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Pinocembrin protects hemorrhagic brain primarily by inhibiting toll-like receptor 4 and reducing M1 phenotype microglia

Lan

Han

et al. 2017

Brain, Behavior, and Immunity

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Neuroinflammation is a major contributor to intracerebral hemorrhage (ICH) progression, but no drug is currently available to reduce this response and protect against ICH-induced injury. Recently, the natural product pinocembrin has been shown to ameliorate neuroinflammation and is undergoing a phase II clinical trial for ischemic stroke treatment. In this study, we examined the efficacy of pinocembrin in an ICH model, and further examined its effect on microglial activation and polarization. In vivo, pinocembrin dose-dependently reduced lesion volume by 47.5% and reduced neurologic deficits of mice at 72 h after collagenase-induced ICH. The optimal dose of pinocembrin (5 mg/kg) suppressed microglial activation as evidenced by decreases in CD68-positive microglia and reduced proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. Pinocembrin also reduced the number of classically activated M1-like microglia without affecting M2-like microglia in the perilesional region. Additionally, pinocembrin decreased the expression of toll-like receptor (TLR)4 and its downstream target proteins TRIF and MyD88. The protection by pinocembrin was lost in microglia-depleted mice and in TLR4lps-del mice, and pinocembrin failed to decrease the number of M1-like microglia in TLR4lps-del mice. In lipopolysaccharide-stimulated BV-2 cells or primary microglia, pinocembrin decreased M1-related cytokines and markers (IL-1β, IL-6, TNF-α, and iNOS), NF-κB activation, and TLR4 expression, but it did not interfere with TLR4/MyD88 and TLR4/TRIF interactions or affect microglial phagocytosis of red blood cells. Inhibition of the TLR4 signaling pathway and reduction in M1-like microglial polarization might be the major mechanism by which pinocembrin protects hemorrhagic brain. With anti-inflammatory properties, pinocembrin could be a promising new drug candidate for treating ICH and other acute brain injuries.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pinocembrin protects hemorrhagic brain primarily by inhibiting toll-like receptor 4 and reducing M1 phenotype microglia

Lan

Han

et al. 2017

Brain, Behavior, and Immunity

Self Cite

180

153

View full text Add to dashboard Cite

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“…These include apocynin [66,67,68], baicalein [69], caffeine [70,71,109], curcumin [72,73,74], niacin [64], nicotine [64], pinocembrin [75,76,110], resveratrol [77,78,79,80,81,111], polyphenols [112], and tanshinone IIA [82,83,84]. However, the number of studies investigating the effects of these agents on neurodegeneration and cognitive performance is limited.…”

Section: Antioxidants Cognitive Decline and Blood-brain Barriermentioning

confidence: 99%

Antioxidants and Dementia Risk: Consideration through a Cerebrovascular Perspective

2016

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A number of natural and chemical compounds that exert anti-oxidative properties are demonstrated to be beneficial for brain and cognitive function, and some are reported to reduce the risk of dementia. However, the detailed mechanisms by which those anti-oxidative compounds show positive effects on cognition and dementia are still unclear. An emerging body of evidence suggests that the integrity of the cerebrovascular blood-brain barrier (BBB) is centrally involved in the onset and progression of cognitive impairment and dementia. While recent studies revealed that some anti-oxidative agents appear to be protective against the disruption of BBB integrity and structure, few studies considered the neuroprotective effects of antioxidants in the context of cerebrovascular integrity. Therefore, in this review, we examine the mechanistic insights of antioxidants as a pleiotropic agent for cognitive impairment and dementia through a cerebrovascular axis by primarily focusing on the current available data from physiological studies. Conclusively, there is a compelling body of evidence that suggest antioxidants may prevent cognitive decline and dementia by protecting the integrity and function of BBB and, indeed, further studies are needed to directly examine these effects in addition to underlying molecular mechanisms.

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Design, Synthesis, and Phenotypic Profiling of Pyrano‐Furo‐Pyridone Pseudo Natural Products

et al. 2019

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Natural products (NPs) inspire the design and synthesis of novel biologically relevant chemical matter,f or instance through biology-oriented synthesis (BIOS). However, BIOS is limited by the partial coverageo fN P-like chemical space by the guiding NPs.The design and synthesis of "pseudo NPs" overcomes these limitations by combining NP-inspired strategies with fragment-based compound design through de novo combination of NP-derived fragments to unprecedented compound classes not accessible through biosynthesis. We describe the development and biological evaluation of pyrano-furo-pyridone (PFP) pseudo NPs,w hichc ombine pyridone-and dihydropyran NP fragments in three isomeric arrangements.C heminformatic analysis indicates that the PFPs reside in an area of NP-like chemical space not covered by existing NPs but rather by drugs and related compounds. Phenotypic profiling in atarget-agnostic "cell painting" assay revealed that PFPs induce formation of reactive oxygen species and are structurally novel inhibitors of mitochondrial complex I.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

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The Natural Flavonoid Pinocembrin: Molecular Targets and Potential Therapeutic Applications

Cited by 118 publications

References 73 publications

Pinocembrin protects hemorrhagic brain primarily by inhibiting toll-like receptor 4 and reducing M1 phenotype microglia

Pinocembrin protects hemorrhagic brain primarily by inhibiting toll-like receptor 4 and reducing M1 phenotype microglia

Antioxidants and Dementia Risk: Consideration through a Cerebrovascular Perspective

Design, Synthesis, and Phenotypic Profiling of Pyrano‐Furo‐Pyridone Pseudo Natural Products

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